تفاعل #1340616

معادلة التفاعل

7-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

triethylamine

(3S,4S)-1-(benzyloxycarbonyl)-3-(tert-butoxycarbonylamino)-4-ethylpyrrolidine

→

title compound

المردود 50.1%

7-[(3S,4S)-3-Amino-4-ethylpyrrolidine-1-yl]-1-[(1R,2S)-2-fluorocyclopropyl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

المردود 50.1%

المذيبات

methanol

ظروف التفاعل

المعالجة

1. 1
   ترشيحAfter filtration
2. 2
   تركيزthe filtrate was concentrated under reduced pressure
3. 3
   workup.DISSOLUTIONThe obtained residue was dissolved in dimethyl sulfoxide (3 mL)
4. 4
   تركيزThe reaction mixture was concentrated under reduced pressure
5. 5
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate (50 mL)
6. 6
   غسيلThe solution was washed sequentially with a 10% aqueous citric acid solution (30 mL), water (30 mL×2), and saturated brine (30 mL)
7. 7
   تجفيفby drying over anhydrous sodium sulfate
8. 8
   ترشيحAfter filtration
9. 9
   تركيزthe filtrate was concentrated under reduced pressure
10. 10
    workup.ADDITIONSubsequently, concentrated hydrochloric acid (2 mL) was added to the obtained residue at room temperature
11. 11
    أخرىthe resultant mixture was transferred to a separatory funnel with water (20 mL)
12. 12
    غسيلby washing by chloroform (30 mL×2)
13. 13
    درجة الحرارةunder cooling with ice
14. 14
    استخلاصthe resultant mixture was extracted with chloroform (100 mL×3)
15. 15
    تجفيفThe combined organic layer was dried over anhydrous sodium sulfate
16. 16
    أخرىthe solvent was removed under reduced pressure
17. 17
    أخرىThe obtained residue was recrystallized from hot ethanol
18. 18
    أخرىdried under reduced pressure

الإجراء التجريبي

A 10% palladium carbon catalyst (27 mg) was added to a solution of (3S,4S)-1-(benzyloxycarbonyl)-3-(tert-butoxycarbonylamino)-4-ethylpyrrolidine (270 mg, 775 μmol) in methanol (7.75 mL), and the resultant mixture was stirred under a hydrogen atmosphere at room temperature for 15 hours. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in dimethyl sulfoxide (3 mL), and 7-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (216 mg, 775 μmol) and triethylamine (130 μL, 930 μmol) were added to the solution, followed by stirring in an oil bath at 65° C. for 8 days. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (50 mL). The solution was washed sequentially with a 10% aqueous citric acid solution (30 mL), water (30 mL×2), and saturated brine (30 mL), followed by drying over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Subsequently, concentrated hydrochloric acid (2 mL) was added to the obtained residue at room temperature, and the resultant mixture was transferred to a separatory funnel with water (20 mL), followed by washing by chloroform (30 mL×2). The pH of the obtained aqueous layer was adjusted to 12.0 with a 10 mol/L aqueous sodium hydroxide solution under cooling with ice. The pH was adjusted again to 7.4, and the resultant mixture was extracted with chloroform (100 mL×3). The combined organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The obtained residue was recrystallized from hot ethanol, and dried under reduced pressure, to thereby yield the title compound as pale yellow crystals (145 mg, 50.1%).

المصدر